Key Points

Rates of moderate or severe long-term effects to normal tissue were low across all treatment groups.

No changes or only minor changes in normal tissue were observed in 88% and 86% of women at the 5- and 10-year marks, respectively.

Moderate/severe late effects to normal breast tissue were higher, however, for patients who received the 5-fraction, 30-Gy regimen. These patients were two to three times more likely to experience moderate/severe instances of breast shrinkage, hardness, fluid buildup, and spider veins.

In a 10-year study of women who received radiation therapy to treat early-stage breast cancer, those receiving fewer, larger individual radiation doses experienced similarly low rates of late-onset side effects as those undergoing conventional radiation therapy. Findings from the multi-institutional FAST clinical trial were presented by Brunt et al at the 60th Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Abstract LBA2).

“This study says it’s possible to find a regimen that would allow early-stage breast cancer patients to be treated only once a week over 5 weeks rather than daily over the same time period,” said Murray Brunt, MD, Professor of Clinical Oncology at University Hospitals of North Midlands and Keele University and lead author of this study. “Findings should help doctors discuss risks and benefits with their patients for various courses of radiation therapy and inform shared decision-making between physicians and patients.”

FAST Trial

The study is a long-term report of the FAST trial, which was designed to assess changes in healthy breast tissue following conventional radiation treatment compared with two shorter regimens that delivered higher doses of radiation in fewer sessions. The trial enrolled 915 women with early-stage invasive breast cancer at 18 centers across the UK from 2004 to 2007.

Initial trial results of the FAST trial, published in Radiotherapy and Oncologyin 2011, indicated that once-weekly, hypofractionated therapy led to similarly low normal tissue effects as conventional therapy at 2 years following treatment. The current study confirms that these similarities persist for an additional 8 years.

“These results support treatment options that are more convenient for patients, resulting in fewer hospital visits and less expensive health services, without increasing the risk of long-term side effects,” added the study’s senior statistician, Joanne Haviland, of The Institute of Cancer Research, London.

Patients in the trial were randomly assigned to 1 of 3 regimens of whole-breast radiation therapy following breast-conserving surgery: conventional treatment with 50 Gy of radiation delivered in 25 daily 2-Gy fractions delivered over 5 weeks; or hypofractionated treatment with 1 of 2 doses: 30 Gy delivered in 5 once-weekly fractions of 6 Gy each, or 28.5 Gy delivered in 5 once-weekly fractions of 5.7 Gy each. After treatment, patients were evaluated annually for effects to healthy breast tissue including skin reactions, hardening of the breast, and changes in breast conformation and size.

Study Findings

Rates of moderate or severe long-term effects to normal tissue were low across all treatment groups. Severe effects were observed in 13 of the 774 women (1.7%) with follow-up data at 5 years, and 9 of the 392 women (2.3%) with follow-up data at 10 years. No changes or only minor changes in normal tissue were observed in 88% and 86% of women at the 5- and 10-year marks, respectively.

Late normal tissue effects were not statistically different between the conventional therapy group and the 5-fraction 28.5-Gy group at 5 years or 10 years following treatment. Moderate/severe late effects to normal breast tissue were higher, however, for patients who received the 5-fraction 30-Gy regimen. These patients were two to three times more likely to experience moderate/severe instances of breast shrinkage (P < .001), hardness (P = .004), fluid buildup (P < .001), and spider veins (P = .02).

Among patients on the conventional, daily-fraction arm, physicians observed normal tissue effects in 7.5% at 5 years and 9.1% at 10 years. By comparison, rates for the 5-fraction 30-Gy arm were 18.0% at 5 years (P < .001) and 18.4% at 10 years (P = .04).

“The profile of adverse effects to normal breast tissue was similar between the 28.5-Gy and 50-Gy groups, but rates were higher after 30 Gy given in 5 fractions over 5 weeks,” said Dr. Brunt. “This disparity is rooted in differences between the two regimens in fractionation sensitivity. The sensitivity of 30 Gy delivered in 5 fractions over 5 weeks was equivalent to a total radiation dose of 57.3 Gy in 2-Gy fractions, whereas 28.5 Gy delivered in 5 fractions over 5 weeks was roughly the same as 52.5 Gy in 2-Gy fractions.” Calculation suggests that 27.75 Gy delivered in 5 fractions over 5 weeks would be equivalent to 50 Gy in 25 fractions over 5 weeks.

Researchers also assessed how the early-stage invasive breast tumors responded to surgery and radiation. The 10-year local relapse rate for all patients in the trial was 1.3% (95% confidence interval = 0.7%–2.3%), with only 10 events reported in total, balanced between the treatment groups. The trial was not designed to test differences in relapse rates between treatment groups.

Following these results, the research team is now investigating radiation therapy with 5 fractions delivered over 5 consecutive days. “As a next step, we want to investigate shortening the radiation therapy schedule to 1 week,” explained Dr. Brunt. “A schedule like this would have significant clinical and practical implications, such as allowing radiation therapy to be integrated more closely with surgery and other therapies.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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